It has been suggested that the production of prostagalndins by the lung may be an important factor in pathogenesis of a variety of pulmonary diseases. Since paraquat, a commonly used herbicide, causes massive lung damage in a number of animal species, the effect of paraquat on the prostaglandin synthesis in the lung was examined. Treatment of guinea pigs with paraquat dichloride (10 mg/kg ip) markedly reduced the capacity of the lung to synthesize various prostaglandins, including prostacyclin, at 24 and 48 hr. This treatment which produced marked alveolar damage including edema, leucocyte infiltration capillary congestion at 24 hr and severe diffused alveolites with obliteration of normal lung architecture at 48 hr.. The same treatment with paraquat induced a marked increase in activity of guanylate cyclase in the lung, indicating the possible involvement of cyclic GMP in proliferative changes in the lung which occur after administration of paraquat.